Design, Synthesis, and Pharmacological Activity of a New Matrix Metalloproteinase-9 Inhibitor

  • O. S. Grigorkevich
  • G. V. Mokrov
  • A. S. Dyabina
  • V. N. Stolyaruk
  • I. B. Tsorin
  • E. O. Ionova
  • S. A. Kryzhanovskii
  • T. A. Gudasheva
  • A. D. Durnev
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The new MMP-9 inhibitor 1-{4-[(4-chlorobenzoyl)amino]phenyl}sulfonyl-L-proline, with a theoretical inhibition constant of IC50 = 4 × 105 M, was constructed on the basis of structural requirements for selective inhibitors of gelatinases. This constructed compound and its close structural analogs were synthesized and these substances were found to have low toxicity, (LD50 > 300 mg/kg). The new inhibitor given p.o. at a dose of 20 mg/kg/day on the background of acute myocardial infarction significantly decreased the content of immunoreactive MMP-9 in plasma in rats, to the level obtained with doxycycline.

Keywords

matrix metalloproteinases gelatinase B MMP-9 inhibitors benzoylamino(phenylsulfonyl)amino acids cardioprotective substances early postinfarct myocardial remodeling 
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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • O. S. Grigorkevich
    • 1
  • G. V. Mokrov
    • 1
  • A. S. Dyabina
    • 1
  • V. N. Stolyaruk
    • 1
  • I. B. Tsorin
    • 1
  • E. O. Ionova
    • 1
  • S. A. Kryzhanovskii
    • 1
  • T. A. Gudasheva
    • 1
  • A. D. Durnev
    • 1
  1. 1.V. V. Zakusov Science Research Institute of PharmacologyMoscowRussia

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